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【结 构 式】 
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【分子编号】35712 【品名】 【CA登记号】 |
【 分 子 式 】C30H36O8 【 分 子 量 】524.61104 【元素组成】C 68.69% H 6.92% O 24.4% |
合成路线1
该中间体在本合成路线中的序号：(XL)The cleavage of the 4-methoxybenzyl group of (XXXIII) with DDQ in dichloromethane/water gives the secondary alcohol (XXXIV), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXV). The cyclization of (XXXV) with AcOH affords the tetracyclic compound (XXXVI), which is silylated at the carbinol group with Tes-OTf and lutidine giving the silyl ether (XXXVII). The oxidation of (XXXVII) with DMP in refluxing benzene affords the carbinol (XXXVIII), which is selectively desilylated and cyclized with TFA in dichloromethane/water giving the pentacyclic compound (XXXIX). The oxidation of the hydroxymethyl group of (XXXIX) with DMP in dichloromethane yields corresponding aldehyde (XL), which is silylated at the remaining OH group with Tbdms-OTf and lutidine in dichloromethane to afford the silyl ether (XLI). The oxidation of the aldehyde group of (XLI) with NaClO2 in tert-butanol/water gives the carboxylic acid (XLII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXIV) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXV) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XXXVI) | 35708 | C36H54O8Si | 详情 | 详情 | ||
| (XXXVII) | 35709 | C42H68O8Si2 | 详情 | 详情 | ||
| (XXXVIII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XXXIX) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XL) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLI) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLII) | 35714 | C36H50O9Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLIV)The selective hydrolysis of (XXXV) with aqueous AcOH gives the alpha hydroxy ketone (XXXVI), which is silylated at the OH group with TBDMS-OTf and lutidine in dichloromethane yielding the silyl ether (XXXVII). The cleavage of the 4-methoxybenzyl group of (XXXVII) with DDQ in CH2Cl2/H2O gives the secondary alcohol (XXXVIII), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXIX). The cyclization of (XXXIX) with AcOH affords the tetracyclic compound (XL), which is silylated at the carbinol group with TES-OTf and lutidine giving the silyl ether (XLI). The oxidation of (XLI) with DMP in refluxing benzene affords the carbinol (XLII), which is selectively desilylated and cyclized with TFA in CH2Cl2/H2O giving the pentacyclic compound (XLIII). The oxidation of the hydroxymethyl group of (XLIII) with DMP in CH2Cl2 yields corresponding aldehyde (XLIV).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 【2】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【3】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXV) | 35703 | C49H74O9Si | 详情 | 详情 | ||
| (XXXVI) | 35704 | C41H54O8 | 详情 | 详情 | ||
| (XXXVII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXVIII) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXIX) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XL) | 40300 | (8S,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-8-(hydroxymethyl)-14-[(E)-6-octenyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C36H54O8Si | 详情 | 详情 | |
| (XLI) | 40301 | (8R,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-14-[(E)-6-octenyl]-8-[[(triethylsilyl)oxy]methyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C42H68O8Si2 | 详情 | 详情 | |
| (XLII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XLIII) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XLIV)The silylation at the remaining OH group of (XLIV) with TBDMS-OTf and lutidine in dichloromethane affords the silyl ether (XLV), which is oxidized at the aldehyde group with NaClO2 in tert-butanol/water giving the carboxylic acid (XLVI). The reaction of (XLVI) with methanesulfonyl chloride and Et3N in THF gives the mixed anhydride (XLVII), which is treated with diazomethane in ethyl ether/THF to yield the diazoketone (XLVIII). The rearrangement of (XLVIII) with Ag2O in DMF/water affords the acetic acid derivative (XLIX), which is condensed with indoline (L) by means of EDC and DMAP in CH2Cl2 to provide the acyl indoline (LI). The desilylation of (LI) with TFA/water in dichloromethane gives the secondary alcohol (LII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLV) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLVI) | 35714 | C36H50O9Si | 详情 | 详情 | ||
| (XLVII) | 35715 | C39H56O9SSi | 详情 | 详情 | ||
| (XLVIII) | 35716 | C37H50N2O8Si | 详情 | 详情 | ||
| (XLIX) | 35717 | C37H52O9Si | 详情 | 详情 | ||
| (L) | 19652 | indoline | 496-15-1 | C8H9N | 详情 | 详情 |
| (LI) | 35718 | (9S,12S,13S,15R,18R)-18-[[tert-butyl(dimethyl)silyl]oxy]-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C45H59NO8Si | 详情 | 详情 | |
| (LII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XL)The cleavage of the 4-methoxybenzyl group of (XXXIII) with DDQ in dichloromethane/water gives the secondary alcohol (XXXIV), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXV). The cyclization of (XXXV) with AcOH affords the tetracyclic compound (XXXVI), which is silylated at the carbinol group with Tes-OTf and lutidine giving the silyl ether (XXXVII). The oxidation of (XXXVII) with DMP in refluxing benzene affords the carbinol (XXXVIII) (1), which is selectively desilylated and cyclized with TFA in dichloromethane/water giving the pentacyclic compound (XXXIX). The oxidation of the hydroxymethyl group of (XXXIX) with DMP in dichloromethane yields corresponding aldehyde (XL), which is silylated at the remaining OH group with Tbdms-OTf and lutidine in dichloromethane to afford the silyl ether (XLI). The oxidation of the aldehyde group of (XLI) with NaClO2 in tert-butanol/water gives the carboxylic acid (XLII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXIV) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXV) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XXXVI) | 35708 | C36H54O8Si | 详情 | 详情 | ||
| (XXXVII) | 35709 | C42H68O8Si2 | 详情 | 详情 | ||
| (XXXVIII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XXXIX) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XL) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLI) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLII) | 35714 | C36H50O9Si | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XLIV)The selective hydrolysis of (XXXV) with aqueous AcOH gives the alpha hydroxy ketone (XXXVI), which is silylated at the OH group with TBDMS-OTf and lutidine in dichloromethane yielding the silyl ether (XXXVII). The cleavage of the 4-methoxybenzyl group of (XXXVII) with DDQ in dichloromethane/water gives the secondary alcohol (XXXVIII), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXIX). The cyclization of (XXXIX) with AcOH affords the tetracyclic compound (XL), which is silylated at the carbinol group with TES-OTf and lutidine giving the silyl ether (XLI). The oxidation of (XLI) with DMP in refluxing benzene affords the carbinol (XLII), which is selectively desilylated and cyclized with TFA in dichloromethane/water giving the pentacyclic compound (XLIII). The oxidation of the hydroxymethyl group of (XLIII) with DMP in dichloromethane yields corresponding aldehyde (XLIV).
| 【1】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 【2】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【3】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXV) | 35703 | C49H74O9Si | 详情 | 详情 | ||
| (XXXVI) | 35704 | C41H54O8 | 详情 | 详情 | ||
| (XXXVII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXVIII) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXIX) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XL) | 40300 | (8S,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-8-(hydroxymethyl)-14-[(E)-6-octenyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C36H54O8Si | 详情 | 详情 | |
| (XLI) | 40301 | (8R,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-14-[(E)-6-octenyl]-8-[[(triethylsilyl)oxy]methyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C42H68O8Si2 | 详情 | 详情 | |
| (XLII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XLIII) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XLIV)The silylation at the remaining OH group of (XLIV) with TBDMS-OTf and lutidine in dichloromethane affords the silyl ether (XLV), which is oxidized at the aldehyde group with NaClO2 in tert-butanol/water giving the carboxylic acid (XLVI). The reaction of (XLVI) with methanesulfonyl chloride and Et3N in THF gives the mixed anhydride (XLVII), which is treated with diazomethane in ethyl ether/THF to yield the diazoketone (XLVIII). The rearrangement of (XLVIII) with Ag2O in DMF/water affords the acetic acid derivative (XLIX), which is condensed with indoline (L) by means of EDC and DMAP in dichloromethane to provide the acyl indoline (LI). The desilylation of (LI) with TFA/water in dichloromethane gives the secondary alcohol (LII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLV) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLVI) | 35714 | C36H50O9Si | 详情 | 详情 | ||
| (XLVII) | 35715 | C39H56O9SSi | 详情 | 详情 | ||
| (XLVIII) | 35716 | C37H50N2O8Si | 详情 | 详情 | ||
| (XLIX) | 35717 | C37H52O9Si | 详情 | 详情 | ||
| (L) | 19652 | indoline | 496-15-1 | C8H9N | 详情 | 详情 |
| (LI) | 35718 | (9S,12S,13S,15R,18R)-18-[[tert-butyl(dimethyl)silyl]oxy]-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C45H59NO8Si | 详情 | 详情 | |
| (LII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 |